Variant chr1-3468917-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014448.4(ARHGEF16):c.842A>G(p.Glu281Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,550,112 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

ARHGEF16
NM_014448.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

Variant links:

Genes affected

ARHGEF16 (HGNC:15515): (Rho guanine nucleotide exchange factor 16) Although the specific function of this protein is not known yet, it is thought to be involved in protein-protein and protein-lipid interactions. [provided by RefSeq, Jul 2008]

ARHGEF16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036803275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARHGEF16	NM_014448.4 linkuse as main transcript	c.842A>G	p.Glu281Gly	missense_variant	5/15	ENST00000378378.9	NP_055263.2	Q5VV41-1B3KTS4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARHGEF16	ENST00000378378.9 linkuse as main transcript	c.842A>G	p.Glu281Gly	missense_variant	5/15	2	NM_014448.4	ENSP00000367629.4	Q5VV41-1
ARHGEF16	ENST00000378371 linkuse as main transcript	c.-23A>G		5_prime_UTR_variant	2/12	1		ENSP00000367622.2	Q5VV41-2
ARHGEF16	ENST00000378373 linkuse as main transcript	c.-23A>G		5_prime_UTR_variant	3/13	1		ENSP00000367624.1	Q5VV41-2
ARHGEF16	ENST00000445297 linkuse as main transcript	c.-23A>G		5_prime_UTR_variant	1/4	3		ENSP00000411936.1	B0QZD3

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000325

AC:

AN:

153854

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000459

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1398060

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

689554

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000336

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000587

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152052

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000788

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.842A>G (p.E281G) alteration is located in exon 5 (coding exon 4) of the ARHGEF16 gene. This alteration results from a A to G substitution at nucleotide position 842, causing the glutamic acid (E) at amino acid position 281 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Benign

0.064

Eigen_PC

Benign

-0.0084

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.032

MetaRNN

Benign

0.037

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.16

Sift

Benign

0.034

Sift4G

Uncertain

0.0040

Polyphen

0.78

Vest4

0.21

MutPred

0.33

Loss of ubiquitination at K284 (P = 0.0597);

MVP

0.39

MPC

0.89

ClinPred

0.57

GERP RS

3.3

Varity_R

0.33

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over